The significance of the senescence pathway in breast cancer progression.

Invasive breast cancer develops through prolonged accumulation of multiple genetic changes. The progression to a malignant phenotype requires overriding of growth inhibition. It is evident that some breast cancers have an inherited basis, and both hereditary and sporadic cancers appear to involve molecular mechanisms that are linked to the cell cycle. Frequently, changes in the molecular pathways with gene deletions, point mutations and/or overexpression of growth factors can be seen in these cancers. Recent evidence also implicates the senescence pathway in breast carcinogenesis. It has a barrier effect towards excessive cellular growth, acting as the regulator of tumour initiation and progression. Later in carcinogenesis, acquisition of the senescence associated secretory phenotype may instead promote tumour progression by stimulating growth and transformation in adjacent cells. This two-edge role of senescence in cancer directs more investigations into the effects of the senescence pathway in the development of malignancy. This review presents the current evidence on the roles of senescence molecular pathways in breast cancer and its progression.